This invention relates to a composition for solid pharmaceutical preparations containing a vitamin D.sub.3 derivative and a process for the preparation thereof, and more particularly to a composition for solid pharmaceutical preparations containing a vitamin D.sub.3 derivative in which mannitol and sugar are used as an excipient.
In general, vitamin D.sub.3 derivatives are labile and apt to be readily oxidized and cause isomerization. It is known that the isomerization of the derivatives readily occurs due to contact with an additive as well as exposure to light and heat (Tetsuya Takahashi and Ryuichi Yamamoto, Journal of the Pharmaceutical Society of Japan, 89, 909 (1969)). Also, in order to stabilize a vitamin D.sub.3 derivative, techniques of incorporating the vitamin D derivative in bile acids, cholesterols or polyvinyl pyrrolidone to prevent oxidation and isomerization of the derivative are proposed (Japanese Patent Application Laid-Open Publication No. 69562/1980, Japanese Patent Application Laid-Open Publication No. 40461/1982, Japanese Patent Application Laid-Open Publication No. 206533/1983 and Japanese Patent Application Laid-Open Publication No. 155309/1984).
As will be noted from the above, vitamin D.sub.3 derivatives are labile to heat and light and apt to be readily oxidized, so that a suitable means such as refrigeration, light shielding, replacement with inert gas or the like is employed to prevent deterioration of pharmaceutical preparations containing a vitamin D.sub.3 derivative.
In particular, 26, 26, 26, 27, 27, 27-hexafluoro-1.alpha., 25-dihydroxycholecalciferol (Kobayashi et al, Chem. Pharm. Bull, 30, 4297 (1982)) prepared by replacing each of six hydrogen atoms at positions 26 and 27 of 1.alpha., 25-dihydroxycholecalciferol with a fluorine atom has a extremely high vitamin D-like activity and is merely contained in a very small amount in solid pharmaceutical preparations. Thus, it is highly required to develop techniques of dispersing a trace unstable component in solid pharmaceutical preparations and stabilize the unstable component in the preparations in order to prevent deterioration of the preparations.
Accordingly, it is highly desirable to provide solid pharmaceutical preparations in which a vitamin D.sub.3 derivative is stabilized and the content of a vitamin D.sub.3 derivative is rendered uniform.